ABSTRACT
The reliability of analysis is becoming increasingly important as point-of-care diagnostics are transitioning from single-analyte detection toward multiplexed multianalyte detection. Multianalyte detection benefits greatly from complementary metal-oxide semiconductor (CMOS) integrated sensing solutions, offering miniaturized multiplexed sensing arrays with integrated readout electronics and extremely large sensor counts. The development of CMOS back end of line integration compatible graphene field-effect transistor (GFET)-based biosensing has been rapid during the past few years, in terms of both the fabrication scale-up and functionalization toward biorecognition from real sample matrices. The next steps in industrialization relate to improving reliability and require increased statistics. Regarding functionalization toward truly quantitative sensors, on-chip bioassays with improved statistics require sensor arrays with reduced variability in functionalization. Such multiplexed bioassays, whether based on graphene or on other sensitive nanomaterials, are among the most promising technologies for label-free electrical biosensing. As an important step toward that, we report wafer-scale fabrication of CMOS-integrated GFET arrays with high yield and uniformity, designed especially for biosensing applications. We demonstrate the operation of the sensing platform array with 512 GFETs in simultaneous detection for the sodium chloride concentration series. This platform offers a truly statistical approach on GFET-based biosensing and further to quantitative and multianalyte sensing. The reported techniques can also be applied to other fields relying on functionalized GFETs, such as gas or chemical sensing or infrared imaging.
ABSTRACT
COVID-19, caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), originated a global health crisis, causing over 2 million casualties and altering human daily life all over the world. This pandemic emergency revealed the limitations of current diagnostic tests, highlighting the urgency to develop faster, more precise and sensitive sensors. Graphene field effect transistors (GFET) are analytical platforms that enclose all these requirements. However, the design of a sensitive and robust GFET is not a straightforward objective. In this work, we report a GFET array biosensor for the detection of SARS-CoV-2 spike protein using the human membrane protein involved in the virus internalisation: angiotensin-converting enzyme 2 (ACE2). By finely controlling the graphene functionalisation, by tuning the Debye length, and by deeply characterising the ACE2-spike protein interactions, we have been able to detect the target protein with an extremely low limit of detection (2.94 aM). This work set the basis for a new class of analytical platforms, based on human membrane proteins, with the potential to detect a broad variety of pathogens, even before their isolation, being a powerful tool in the fight against future pandemics.
